Rare Disease Pfizer Confidential
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Rare Disease Pfizer Confidential 1
Forward-Looking Statements and Other Notices Our discussions during Pfizer’s Investor Day include forward-looking statements about our anticipated future operating and financial performance, business plans and prospects; expectations for our product pipeline, in-line products and product candidates, including anticipated regulatory submissions, data read- outs, study starts, approvals, revenue contribution, growth, performance, timing of exclusivity and potential benefits; manufacturing and product supply; our efforts to respond to COVID-19, including our investigational vaccine candidate against SARS-CoV-2 and our investigational protease inhibitor, and our expectations regarding the impact of COVID-19; our ability to successfully capitalize on growth opportunities and prospects; plans for and prospects of our acquisitions and other business development activities, including our proposed transaction with Mylan N.V. (Mylan) to combine Upjohn and Mylan to create a new global pharmaceutical company; plans relating to share repurchases and dividends; and other statements about our business, operations and financial results that are each subject to substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Among other things, statements regarding revenue and earnings per share growth; the development or commercial potential of our product pipeline, in-line products, product candidates and additional indications, including expected clinical trial protocols, the timing of the initiation and progress of clinical trials and data read-outs from trials; the timing for the submission of applications for and receipt of regulatory approvals; expected breakthrough, best or first-in-class status, blockbuster status of our medicines or vaccines; and the impact of anticipated improvements to our clinical operation performance are forward-looking and are estimates that are subject to change and clinical trial and regulatory success. These statements are subject to risks, uncertainties and other factors that may cause actual results to differ materially from past results, future plans and projected future results. Additional information regarding these and other factors can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2019 and in our subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information and Factors That May Affect Future Results”, as well as in our subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at www.sec.gov and www.pfizer.com. Potential risks and uncertainties also include the impact of COVID-19 on our sales and operations, including impacts on employees, manufacturing, supply chain, marketing, research and development and clinical trials. The forward-looking statements in these presentations speak only as of the original date of the presentation and we undertake no obligation to update or revise any of these statements. Today’s discussions and presentations are intended for the investor community only; they are not intended to promote the products referenced herein or otherwise influence healthcare prescribing decisions. All trademarks in today’s presentations are the property of their respective owners.
Rare Disease Leadership Team
Suneet Varma Brenda Cooperstone, MD Seng Cheng, PhD
Global President, Chief Development Officer, Chief Scientific Officer,
Rare Disease Rare Disease Rare Disease
3
Leading Innovation in Rare Disease Through Focused Strategy
A Leading In-Line Portfolio Expand through Launch Scale to Innovate & Accelerate
Rare Hematology Rare Cardiology End-to-End Capabilities
Rare Endocrine/Metabolic Rare Neurology in Gene Therapy
3 Gene Therapy
Manufacturing Sites
7 Products in
Clinical Development 3 Products in
Clinical Development
$800M Investment
>1,000 Colleagues Across ~100 Countries
4
Robust Rare Disease Pipeline With 6 New Molecular Entities
in Phase 3 by Year End 2020
Rare Endocrine/
Rare Hematology Rare Neurology Rare Cardiology
Metabolic
In line
Growth Hormone Duchenne Muscular LMNA-related Dilated
Hemophilia B
Deficiency (Somatrogon) Dystrophy Cardiomyopathy
(p38 MAPK Inhibitor)
Phase 3* Hemophilia A
Pan Hemophilia (Marstacimab)
Sickle Cell Disease
Achondroplasia (Recifercept) ITP/CIDP** (IVIG Mimetic)
(E-Selectin antibody)
Phase 1 & 2
Sickle Cell Disease
(HbS Modulator)
Selected Wilson Disease
Amyotrophic Lateral
Rare Cardiac Disorders
Pre-Clinical Sclerosis
* Phase 3 pending initiation for Hemophilia A and Duchenne Muscular Dystrophy
** Idiopathic thrombocytopenic purpura/ chronic inflammatory demyelinating polyneuropathy Gene Therapy
5
Robust Rare Disease Pipeline With 6 New Molecular Entities
in Phase 3 by Year End 2020
Rare Endocrine/
Rare Hematology Rare Neurology Rare Cardiology
Metabolic
In line
Growth Hormone Duchenne Muscular LMNA-related Dilated
Hemophilia B
Deficiency (Somatrogon) Dystrophy Cardiomyopathy
(p38 MAPK Inhibitor)
Phase 3* Hemophilia A
Pan Hemophilia (Marstacimab)
Sickle Cell Disease
Achondroplasia (Recifercept) ITP/CIDP** (IVIG Mimetic)
(E-Selectin antibody)
Phase 1 & 2
Sickle Cell Disease
(HbS Modulator)
Selected Wilson Disease
Amyotrophic Lateral
Rare Cardiac Disorders
Pre-Clinical Sclerosis
* Phase 3 pending initiation for Hemophilia A and Duchenne Muscular Dystrophy
** Idiopathic thrombocytopenic purpura/ chronic inflammatory demyelinating polyneuropathy Highlighted in today’s presentation Gene Therapy
6
Growing Leadership in Rare
Cardiology
Brenda & Harvey
7
Growing Leadership in Rare Cardiology
• Vyndaqel / Vyndamax for ATTR-Cardiomyopathy
In line • Approved US Q2 2019 / EU Q1 2020
• 25 global submissions completed; 9 more planned through 2021
• PF-07265803 for Dilated Cardiomyopathy with lamin A/C gene mutation
Phase 3
• Phase III study enrolling
Pre-Clinical • Gene therapy for rare cardiac disorders
8
Driving Treatment and Disease Understanding, Early Diagnosis to
Solidify Leadership in Transthyretin Amyloid Cardiomyopathy (ATTR-CM)
Tafamidis 80 mg Demonstrated 30% Greater Commitment to Understanding Prevalence
Survival Benefit Compared with 20 mg1 and Increasing Early Diagnosis
Phase 3 ATTR-ACT Combined with • Participants with Left Ventricular Hypertrophy of
Long-term Extension Study and 61mg
Median follow-up 51 months Hazard ratio (95% CI) Unknown Etiology (N=1500)
Study Initiated Q3 2018 in EU
Unadjusted 0.700 (0.501, 0.979)
Age adjusted 0.612 (0.433, 0.865) • Participants with Heart Failure with Preserved
NT-proBNP adjusted 0.639 (0.455, 0.898) Ejection Fraction (N=2000)
Study Initiation Q4 2020
6MWT adjusted 0.701 (0.496, 0.991)
Age/NT-proBNP/
0.571 (0.395, 0.827) • ATTR-CM Suspect & Detect
6MWT adjusted
0.4 0.8 1.6
• Artificial Intelligence (AI) Machine Learning Model
Favors 80 mg Favors 20 mg
1 Damy, T, et al. European Society of Cardiology-Heart Failure Congress. June 2020.
9
PF-072658031 – p38 MAPK Inhibitor in Development for
LMNA-related Dilated Cardiomyopathy (DCM)
• Loss of functional lamin proteins in the setting of
Disease Overview LMNA DCM associated with p38 MAPK activation4
• A potent and selective, oral small molecule inhibitor
100+ known mutations in lamin A/C gene of the p38 MAPK pathway
• Normalizes left ventricular morphology and
~70% have cardiac death, heart transplant or improves function in the LMNAN195K mouse model5
major cardiac event by age 452
No disease specific treatment options
US prevalence estimate 50K3
(6% of I-DCM); ~10% diagnosed Normal LMNAN195K Mutant + LMNAN195K Mutant +
Placebo PF-07265803
1 Previously ARRY-371797 4 Muchir A, et al. Hum Mol Genet. 2012 Oct 1; 21(19).
2 Taylor MR, et al. J Am Coll Cardiol. 2003 Mar 5.
5 Saqib A, et al. Circulation 2011;124:A15685.
3 Hershberger RE, et al. Nat Rev Cardiol. 2013 Sep;10(9).
10Phase 3 Study Initiated in Patients with LMNA-related DCM Based
on Encouraging Phase 2 Results
Phase 21 Demonstrated Sustained Improvement
Ongoing Phase 3 Study
on 6-Minute Walk Test Distance (6MWD)
Primary Endpoint: 69 meters mean absolute change • Randomized, placebo-controlled 24-week study
from baseline at 12 weeks in patients with LMNA-related DCM (N=160)
100
Change from BL in 6MW Distance
Mean 6MWD at Baseline = 321 m • Primary endpoint: change from baseline in
75
6MWD at 12 weeks
(Mean )
50 • Currently 30 patients enrolled
25 • Top line results anticipated in 2023
0
-10.00 0.00 10.00 20.00 30.00 40.00 50.00 60.00 70.00 80.00
Time Point (weeks)
-25
N=12 N=9 N=8 N=8 N=8 N=5
1 C. MacRae, M.R.G. et al. European Heart Journal, Volume 37, Issue suppl_1, 1 August 2016.
Note: 12 patients enrolled. 8 patients that completed 48 weeks of treatment continued to receive study drug under a continuing treatment protocol. There were no deaths during the study.
11An Industry Leading End-to-End
Gene Therapy Platform
Brendan & Colleen
12An Industry Leading End-to-End Gene Therapy Platform
Positioned to Launch Three Transformational Gene Therapies by 2023
Discover Develop Deliver
• 10 preclinical rAAV programs in • Three Phase 3 programs • $800M investment in in-house
rare cardiology, hematology, expected in 2020 manufacturing which aims to fully
neurology & metabolic diseases supply global demand
• Extensive experience enabling
• Partnerships & acquisitions to acceleration • Leader in shaping global policy
complement internal pipeline
• Clinical trial site footprint supports • Innovative solutions to address
• First to manufacture rAAV at global gene therapy trials access and affordability
2,000L bioreactor scale using challenges
HEK293 cells • Early and active engagement of
patients and regulatory authorities
13Fidanacogene elaparvovec: Over 4 Years of Follow-up Gene
Therapy for Hemophilia B Patients
WW prevalence ~88K; US/JP/EU ~17K1
ABR = 0.4 ABR = 0.8 ABR = 0.4 ABR = 0.0
Projected 2022 Global Market Size ~$2B2
FDA Breakthrough, RMAT & EMA Prime
designations
Phase 1/2a and Long-Term Follow-Up (LTFU)
• 15 patients with follow-up of up to 4.5 years
• Mean ABR3 ofGiroctocogene fitelparvovec: Potential Best-in-Class Gene
Therapy for Hemophilia A Patients
WW prevalence ~400K; US/JP/EU ~78K1
#
Projected 2023 Global Market Size ~$11B2
FDA Fast Track & RMAT designations
Phase 1/2
#
• 11 patients across 4 doses with up to 85 weeks of
follow-up at Phase 3 dose
• Mean ABR3 of 0 & AIR4 of 0
• 1 SAE that resolved within 24 h; ALT elevations
managed with steroids
Mean Factor VIII activity from week 9 to week 52 (based on group mean)
Data cut July 2020 Phase 3
* mean FVIII level at the given study week
# n=4 due to missed visit at this timepoint • Prospective lead in trial started 2019
Time points up to week 5 are n = 1,2,3,4,4,4, respectively. All others are n = 5 except where noted.
• Planning to dose first subject in 2020
Mean FVIII activity 71% (CA) from week 9-52 with • Pivotal trial readout planned for 2022
3E13 vg/kg dose 1 Ann Intern Med. 2019, 171:540-546.
Patients with data beyond 52 weeks show consistent FVIII levels 2 EvalutePharma Aug 2020.
3 ABR: annualized bleeding rate;
4 AIR: annualized infusion rate beyond protocol defined allowance of prophylaxis.
15DMD Gene Therapy: No SAEs Observed in Additional
9 Boys Dosed
Low Dose High Dose
WW prevalence ~140K; US/EU ~30K1
Projected 2023 Global Market Size ~$4B2
Phase 1b
• Dosed additional 9 boys at high dose (2E14 vg/kg3)
since ASGCT4 (18 total patients), 3 with drug from
commercial manufacturing process
• No SAEs observed with modified immunomodulatory
and monitoring regimen
Phase 3
• Pivotal trial in ambulatory patients planned first subject
dose in 2020
Preliminary signs of efficacy include mini- • Interim analysis anticipated in 2022
dystrophin expression, reduced serum CK and
fat fraction on MRI, and improved NSAA scores 1 Crisafulli et al. Orphanet Journal of Rare Diseases, 2020, 15:141.
2 EvaluatePharma Aug 2020.
3 2E14 vg/kg by the transgene method is approximately equivalent to 3E14 vg/kg by the ITR method, used in the
initial part of the study.
4 Binks, M. AMERICAN SOCIETY OF GENE & CELL THERAPY. 23rd Annual Meeting (May 12-15, 2020).
16Gene Therapy for Wilson Disease IND Planned in 2020
Widespread Decrease in Copper Diagnosed prevalence ~21K US/EU1
in VTX-801-treated Liver
Projected 2026 Global Market Size ~$500M2
• Wilson disease is a chronic, life-threatening disease
caused by aberrant accumulation of copper in liver,
brain and other vital organs
Untreated Treated
• VTX-801 (Vivet Therapeutics), an AAV vector encoding
Dose-dependent Restoration of Normal Biliary/Fecal ATP7B, restores copper homeostasis and reverses liver
Copper Excretion pathology in mouse model of Wilson disease
64Cu tracer in feces 72 hours after IV administration
• IND submission anticipated in 2020
%Injected Dose in Feces
40 Wild-type mice
30 Wilson disease mice • BLA submission planned for 2025
at 72 Hours
WD + VTX-801 5E11 vg/kg
20
WD + VTX-801 1.5E12 vg/kg
10 WD + VTX-801 5E12 vg/kg
WD + VTX-801 1.5E13 vg/kg
0 1 Am J Cardiol., 2017, 8:25 and Clinics and Res in Hepatol and Gastroenterol., 2018, 42:7-63
Journal of Hepatology 2018, 68:1086–1106 2 EvaluatePharma Aug 2020
72
17Leader in Gene Therapy Manufacturing – Building for Growth
~300,000 sq ft with Capacity to Fully Supply
All Gene Therapy Programs in Pipeline,
including DMD at Launch
Grade Scale
Kit Creek, NC
Research &
Development
GLP 10-250L
Early Clinical
~80,000 sq ft
GMP 2 x 500L
Durham, NC Pivotal Clinical &
Commercial GMP 3 x 2,000L
~40,000 sq ft
Commercial
>170,000 sq ft
GMP 8 x 2,000L
Sanford, NC
18Framing the Future Opportunity
Michael
19Significant Clinical and Commercial Opportunities: Rare Cardiology
LMNA-related Dilated Cardiomyopathy
Vyndaqel/Vyndamax
(p38 MAPK Inhibitor)
50K US total prevalence1 100K US total prevalence3
Peak Diagnosis Rate Current Diagnosis Rate
~35% (7-10% at launch) 15% (1% at launch, >35% peak)
40-45% Treatment Eligible2 ~85% Seek Treatment
50-70% Access (peak) ~60% Access (current)
Near Term Competitor Near Term Competitor
1 (at launch) 0 (when launched)
$0.5-1B Potential global annual peak revenues >$1B Potential 2020 Sales
1 Hershberger RE, et al. Nat Rev Cardiol. 2013 Sep;10(9).
2 Includes NYHA Class II/III patients with an ICD or CRT implant.
3 PFE Internal Analysis.
20Significant Clinical and Commercial Opportunities: Gene Therapies
Hemophilia B Hemophilia A
~17K US / JP / EU total prevalence1 ~78K US / JP / EU total prevalence1
60-65% Target Population (moderate & severe) 60-65% Target Population (moderate & severe)
~30% Eligibility2 ~30% Eligibility2
>80% Access (peak) >80% Access (peak)
1-2 Near Term Competitors 2 Near Term Competitors
$0.5-1B Potential global peak revenue >$1B Potential global peak revenue
Gene Therapy
1 Ann Intern Med. 2019, 171:540-546.
2 Gene therapy is expected to have clinical eligibility requirements such as a lack of neutralizing antibodies and liver disease. Hemophilia gene therapy is expected to
require moderate or severe disease and an absence of known history of inhibitors. Hemophilia gene therapy is expected to be available for adults initially, and for a 21
broad age range over time. Patient intent to seek treatment is included.Significant Clinical and Commercial Opportunities: Gene Therapies
Duchenne Muscular Dystrophy Wilson Disease
30K US / EU total prevalence1 21K US / EU total prevalence4
Target Population (failing therapy plus
56% Target Population (boys ages 4-18)2 15-20% those transitioning from stable-to-fail)
75-85% Eligibility3 65-70% Eligibility3
>75% Access (peak) >80% Access (peak)
1 Near Term Competitor 1 Near Term Competitor
>$2B Potential global annual peak revenues $0.5-1B Potential global annual peak revenues
Gene Therapy
1 Crisafulli S., Sultana, J., Fontana, A. et al. Orphanet J Rare Dis 15, 141 (2020). Annual incidence is ~900 patients in US / EU and a similar proportion of male births globally.
2 Of the total prevalence, 31% are ambulatory boys aged 4-18 and 25% are non-ambulatory boys aged 4-18.
3 Gene therapy is expected to have clinical eligibility requirements such as absence of neutralizing antibodies. 22
4 Am J Cardiol., 2017, 8:25 and Clinics and Res in Hepatol and Gastroenterol., 2018, 42:7-63.Our Robust Pipeline Aims to Make a Profound Impact on Pfizer
and the Lives of the Patients We Serve
2019/2020 2021 2022 2023 2024 2025
Vyndaqel
Pfizer Rare Disease 1H 2020 Revenue of $1.3B, +36%G*
* Operational growth excluding FX
23Our Robust Pipeline Aims to Make a Profound Impact on Pfizer
and the Lives of the Patients We Serve
2019/2020 2021 2022 2023 2024 2025
Growth Hormone Duchenne Pan Hemophilia LMNA-related
Vyndaqel Deficiency Hemophilia B Muscular (Marstacimab) Dilated
(Somatrogon) Dystrophy Cardiomyopathy
(p38 MAPK
Inhibitor)
Hemophilia A
Achondroplasia
(Recifercept)
Wilson
Disease**
Poised for at Least 1 Launch per Year*
* On Average Gene Therapy
** Expected BLA filing in 2025
24Q&A
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